Total Intravenous AnesthesiaTotalIntravenous … Intravenous AnesthesiaTotalIntravenous Anesthesia A Rational Approach to Anesthetic Management Michael Rieker, DNP, CRNA Di t N A th

Total Intravenous AnesthesiaTotal Intravenous Anesthesia

A Rational Approach to Anesthetic Management

Michael Rieker, DNP, CRNADi t N A th i PDirector, Nurse Anesthesia Program

Wake Forest Baptist Medical Center

Objectives

Review drugs and methods in TIVA Di h f l h id d d i i t ti fDiscuss how propofol has aided administration ofTIVADescribe different equipment that makesDescribe different equipment that makesadministration of TIVA safe and effectiveList new drugs and drug combinations that are used to improve TIVAOutline medical conditions, disease processes and types of surgery that lend themselves to TIVA for GAtypes of surgery that lend themselves to TIVA for GADiscuss contraindications to TIVA for GA

Drug administration

�Intravenous agents administered by manual bolus on a dose/kg basis is gprobably as old-fashioned as administration of volatileas administration of volatileagents by the Schimmelbusch mask �Schimmelbusch mask.Armin Holas MD, University of Graz, Austria.

Why Intravenous anesthetics?

SafetyHemodynamic controlHemodynamic controlRapid titrationAvoid vasodilatation, expansion of , pgas cavitiesReduced PONVOccupational exposureOccupational exposureSmooth emergence, less hangoverAvoid MH riskCost benefit?

Why Intravenous Anesthetics?

Improved mucociliary transportp y pLedowski. Anesth Analg. 2006;102(5):1427-30.

Reduced PONVRohm. Acta Anaesth Scand. 2006 50(1):14-8.

Less effect on hepatic enzymesp yRohm. Europ J Anaesth. 2005 ;22(3):209-14.

Advantages of TIVA

Improved V/Q matchingPraetel. Anesth Analg. 2004; 99(4):1107-13

Reduced stress response. L d ki A th A l 2005 101(6) 1700 5Ledowski Anesth Analg. 2005;101(6):1700-5.

Improved surgical field (bleeding)Wormald P Am J Rhinology 2005;19 (5): 514Wormald, P, Am J Rhinology 2005;19 (5): 514.

Volatiles assoc. with increased inflammation and decreased immune functionand decreased immune function

Kurosawa Curr Opin Anaesthesiol. 2012;25(3):376.

Optimal technique for neuroanesthesia

Improved extent and duration of cerebral metabolic suppressionsuppression.

Yoon, Kim, & Kim. J Neurosurg Anesthesiol 2012 24(2):146.

Improved CPP, less interference with SSEP, MEP, AEP; Minimal post-op side-effects; potential neuroprotective effects via antioxidant properties.

Hans, P, Current Op Anaes. 2006;19(5):498-503.p ( )

Better preservation of cerebral autoregulation vs. volatile

Ishikawa, Masui. 2003;52(4):370-7

McCulloch Anesthesiology. 2007;106(1):56-64

Not a panacea

+ Titratable, but no diff in shivering, PONV HTNPONV, HTN.

Wong AY. Eur JAnaes 2006;23(7):586-90

No diff in pain; more shivering with TIVANo diff in pain; more shivering with TIVA.Naito, Aya. Comparative study of anesthesia with remifentanil VS fentanyl in terms of postoperative pain

d hi i M i 2009 58 (1) 77and shivering. Masui 2009;58 (1), p. 77.

Cost. (But less PONV)R h KD A t A th i l i S di i 2006 50(1) 14Rohm KD. Acta Anaesthesiologica Scandinavica. 2006;50(1):14-8

Not a panacea

Pre-conditioning/tissue protection from l til i i id ff tvolatiles is a nice side-effect. Landoni, G. "Reducing perioperative myocardial infarction with anesthetic drugs and techniques". Current drug targets 2009;10 (9), p. 858.F ä d f J I t f diti i t l th ti i d dFrässdorf, Jan. Impact of preconditioning protocol on anesthetic-inducedcardioprotection in patients having coronary artery bypass surgery. The Journal of thoracic and cardiovascular surgery 2009;137 (6), p. 1436.

No differences between TIVA and inhalational anesthesia groups with regard to duration of anesthesia, time to discharge from the PACU, bleeding, or incidence offrom the PACU, bleeding, or incidence ofadverse events.

Vlessides, M. Anesthesiology News (07/01/12) Vol. 38, No. 7

Why infusions?

Avoid over and undershoot of dosageAvoid latency in reaching effect siteAvoid latency in reaching effect siteReduce workload intraoperativelyContinuous infusions reduce total drug usage by 25-Continuous infusions reduce total drug usage by 2550%More rapid awakeningLess respiratory depressionDischarge times reduced 30%1

1White PF. Use of continuous infusion versus intermittent bolus administration of fentanyl or ketamine during outpatientWhite PF. Use of continuous infusion versus intermittent bolus administration of fentanyl or ketamine during outpatientanesthesia. Anesthesiology. 59(4):294-300, 1983.

Why infusions?

Avoid over and undershoot of dosageAvoid latency in reaching effect site

Over and undershoot of dosage

Sneyd J R Rigby JonesSneyd J R , Rigby-JonesA E Br. J. Anaesth. 2010;105:246-254

Latency in reaching effect site

Calculated blood and effectblood and effectsite (brain) concentrations following thefollowing thebolus administration of propofol 2 5propofol, 2.5mg/kg over 60 seconds

Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. P. 3.

Latency in reaching effect siteLatency in reaching effect site

Sneyd J R , Rigby-Jones A E Br. J. Anaesth. 2010;105:246-254

Why infusions?

Reduce workload intraoperativelyR d t t l d b 25 50%Reduce total drug usage by 25-50%

Why infusions?

More rapid awakeningLess respiratory depressionLess respiratory depression

Why infusions?

Discharge times reduced 30%White PF. Anesthesiology. 1983;59(4):294-300.

Patients met PACU dischargePatients met PACU dischargecriteria 30 minutes faster with TIVAMontes. Journal of Clinical Anesthesia 2002;14(5):324-8.

Reliability of discharge improvement

Faster readiness, but discharge and cost i d di tsavings are depending upon system

M Féli R (2002) "C i f l iMontes, Félix R (2002). "Comparison of total intravenous anesthesia and sevoflurane-fentanyl anesthesia for outpatient otorhinolaryngeal surgery." Journal of clinical anesthesia, 14 (5), p. 324.

Why now?

Historical perspectiveInhalation anesthesiaInhalation anesthesia

Good open drop ether mask

Strength of pulse

Better concentration-controlled vaporizers

Deliver MAC level

Best RGM, neuromonitors

Titrate to effect-site concentration and response

Why now?

Historical perspectiveIntravenous anesthesiaIntravenous anesthesiaGood IV bolus Estimate time for

recovery, based on βt1/2

Better Infusion pump Titrate according to context-specific half-time

Best Rapid recovery drugs, t t t ll d

Titrate to effect-site t ti dtarget-controlled

infusion pumpsconcentration andresponse

TIVA equipment

Propofol: wonder drug of the 90’s

Recovery profile of propofolRecovery profile of propofolStages of recovery after anesthesia

Early (emergence)- Rapid and predictable

Intermediate- Early return of cognitive and psychomotor function. Early time to discharge (?)y g ( )

Brady. AANA Journal. 2005;73(3):207-10

Low incidence of PONVLow incidence of PONVPurhone. Journal of Clinical Anesthesia. 2006;18(1):41-5.

Frequency of Side Effects withFrequency of Side-Effects withPropofol

5.2Pain on Inj

1.3

1.9

Excitement

N/V

0 3

0.4

1.1

Pain

Brady

Hypotension

0.3

0.3

HTN

Pain

0 2 4 6

McLeskey et. al. Anesth Analg 1993;77:S3-9

Reduced risk of postoperative vomitingReduced risk of postoperative vomitingMeta-analysis of studies: propofol vs volatiles

Allinhalational

agentsIsoflurane

(maintenance)Desflurane

or sevoflurane

2 0

1.0

agents (maintenance)(maintenance)

2.3Reduction in risk of

3.0

2.0

3.7 3.7

vomitingafter ‘Diprivan’(induction and maintenance)

4.06 studies

p = 0.003

maintenance)

n = 4,074

70 studiesp < 0.0001

42 studiesp < 0.0001 Sneyd JR et al.

Sneyd JR et al. Eur J Anaesthesiol;1998, 15(4), pp 433-445

Why now?

S ifi i di tiSpecific indicationsfor TIVA

Need for precision controlAi dAirway proceduresRemote locationsMH susceptibleNeurosurgeryNeuro monitoringPONV risk

Effect on PONV

PONV similar between Propofol TIVA and Sevo + Dolasetron in high risk patients LateSevo + Dolasetron in high-risk patients. LatePONV was worse in TIVA group.

White, British Journal of Anaesthesia. 98(4):470-6, 2007

PONV similar between TIVA without anti-emetic and volatile + anti-emetic

Paech Anaesth Intensive Care 30:153�9

TIVA (without N2O) equally effective as any anti emetic as independent factor reducinganti-emetic as independent factor reducingPONV

Apfel N Engl J Med 350:2441�51

Effect on cancer recurrence

Volatile anesthetics inhibit natural killer cells and T lymphocytesand T lymphocytesVolatiles also inhibit lymphocyte functions

such as proliferation and cytokine productionsuch as proliferation and cytokine production.Propofol and COX-2 inhibitors may deter

tumor growth & metastasistumor growth & metastasis.Kurosawa, S. Anesthesia in patients with cancer disorders. Curr Opin Anaes. 2012. 25(3):376-84.

Disadvantages

Acquisition costsC ll d b iControlled substance accountingSet-up and use greater workload than

ivaporizersEarly or late respiratory depressionO ffOpioid side-effects- biliary, muscle rigidity,

GI motility, pruritusAd t if IV li di t dAdverse events if IV line disrupted

Infusion administration

Good IV bolus Estimate time for recovery, based on βt1/2

Better Infusion pump Titrate according to context-specific half-time

Best Rapid recovery drugs Titrate to effect siteBest Rapid recovery drugs, target-controlled infusion pumps

Titrate to effect-siteconcentration and response

Forget about elimination half-life

A useless measure to guide anesthetic administrationadministrationAs many half-lives as distribution

compartmentscompartmentsTakes no account of time course at effect

sitesitePentothal- half-life = hours

duration = depends on administration du a o depe ds o ad s a oi.e., depends on CONTEXT

Open three-compartment PK model

Context-sensitive half-time

Duration of a drug�sdrug seffects depends on

it�way it�s administered

Hughes MA. Glass PS. Jacobs J:. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 76(3):334-41, 1992.

Context-sensitive half-time

Sneyd, Recent Advances in Intravenous Anaesthesia. Br J Anaesth 2004 93(5):725-736

Context-sensitive alterations in propofol kinetics

Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. p. 10.

Context-sensitive half-time- Midaz.

Comparison of context‐sensitive half‐times forremimazolam and midazolam.Midazolam doses = 0.075mg/kg/h; remimazolam doses= 50 mg/h.Anesthesia & Analgesia.115(2):284‐296, August 2012.

Context-sensitive half life vs.half life vs.necessarydecreasedecrease

Shafer SL. Varvel JR: PharmacokineticsPharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 74(1):53-63, 1991.

Key effect site concentration levels

Fentanyl Alfentanil SufentanilInduction and IntubationThiopental 3-5 ng/ml 250-400 0.4-0.6O /N O l 8 10 400 750 0 8 1 2O2/N2O only 8-10 400-750 0.8-1.2MaintenanceN O/Vapor 1 5 4 100 300 0 25 0 5N2O/Vapor 1.5-4 100-300 0.25-0.5O2/N2O only 1.5-10 100-750 0.25-1.0O2 only 15-60 1000-4000 2-8O2 only 15 60 1000 4000 2 8Adequate Ventilation

1.5 125 0.25

Context-sensitive half life vs. necessary decrease

SufentanilSufentanilng/ml

MaintenanceMaintenance

N2O/Vapor 0.25-0.5

O /N O only 0 25 1 0O2/N2O only 0.25-1.0

O2 only 2-8

Ventilation 0 25

Shafer SL. Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 74(1):53-63, 1991.

Ventilation 0.25

But that’s the old-fashioned way…

Target-controlled infusions eliminate all that thinkingthinking�Computer-driven infusion pumps are programmed with pharmacokinetic data for p g pspecific drugs in a range of patient types. The anesthetist sets the desired blood level, and the p mp does the restand the pump does the rest.

TCI equipment

TCI equipment

Key components of a TCI system

Pharmacokinetics � a validated model with specific parameters for drugAlgorithm(s) to control infusion rate�Control unit� i.e. software and

microprocessors for aboveInfusion pumpUser interface for input of patient data and

target blood concentration

Measured versus calculated blood propofolMeasured versus calculated blood propofolconcentrations during ‘Diprifusor’ TCI administration of propofol in 46 patients.

Russell, D. Practical ,Aspects of Target-Controlled Infusion. Anaesthesia RoundsRoundsOxfordshire, UK, TMG Healthcare Communications Ltd. P. 3.

Diprifusor

Software program Commercially available

�Diprifusor� TCI systems. (a) Graseby 3500.(b) Vial Medical �Master TCI�( ) Alaris IVAC TIVA TCI(c) Alaris IVAC TIVA TCI(d) Terumo Terufusion® TE-

372 TCI TIVA

Loading dose schemes by Diprifusor

Russell, D. Practical Aspects of Target-Controlled Infusion. A th i R d O f d hi UK TMG H l hAnaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. P. 7

“Cardiac” induction by Diprifusor

Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. p. 8.

TCI safety mechanisms

Validated pharmacokineticsCompensation for interrupted infusionAutomatic shutdown in case of malfunctionElectronic tags on pre-filled syringes

(diprivan) to prevent wrong-drug in pump

Tagged prefilled syringes for use withTagged, prefilled syringes for use with‘Diprifusor’ target-controlled infusion systemsy

TCI Displays

TCI Displays

TCI Evaluation

Inaccuracies

Limits: age 16-100 for conventional programs. Weight 30-150 kgWeight 30 150 kgDoes not account for ethnopharmacology (cannot distinguish a Kenyan African from an Italian)Head injuryConcomitant medsNo problem

HypoalbuminemiaRapid fluid adminp

Practical application of TIVA

Select drugs to be used Timing is everything- consider effect site peak

and Co-inductionHigher index of vigilance for recall- reduce

muscle relaxation, awareness monitorf fTitrate infusions based on context-specific

half-time

Drug combinations for TIVA

Opioid infusion schemes

Drug Plasma Target Conc

( / l)

Bolus µg/kg

Infusion Rate µg/kg/min

Use

(ng/ml)

Fentanyl 1 3 0.20 Bal4 10 0 70 N 0/narc4 10 0.70 N20/narc

Alfentanil 40 20 0.25 Analg160 80 1 0 Bal/N20160 80 1.0 Bal/N20

Sufentanil 0.15 0.15 0.003 Bal0.5 0.5 0.01 N20/narc2

Remifentanil 6 1 0.02 analg15 1-2 0.4-1.0 N20/narc

Propofol context-sensitive dosing

Propofol only TIVA: Induce 2-2.5mg/kg, then infuse:infuse:

150-300 µg/kg/min first 10 minutes 120-240 10 min to 2 hours120-240 10 min to 2 hours75-150 beyond 2 hours

Propofol + opioid: Induce 1 5-2mg/kg thenPropofol opioid: Induce 1.5 2mg/kg, then100-150 first 10 minutes 90-140 10 min to 2 hours75-125 beyond 2 hours

Ketamine infusion dosing

Induction: 0.75-2mg/kgInfusion 1-2 mg/kg/hrMidazolam 3-5 mg load, then 0.25 µg/kg/min

Pre-mixed maintenance infusion400 mg ketamine + 4mg midazolam in 100ml saline400 mg ketamine + 4mg midazolam in 100ml saline

Infuse at 0.5 x weight in kg = ml/hr = 2mg/kg/hr ketamine = 0.33 µg/kg/min midazolam

Propofol-Ketamine infusion

Extensive use in outpatient (office) settings with outstanding track record for safety and lack ofoutstanding track record for safety and lack ofside-effects.

Mix ketamine 2mg/ml of propofolInduce with 1-2mg/kg propofol in mixtureg g p pGive additional 0.5-1mg/kg ketamine after asleepInfuse 140-200 µg/kg/min first 10 minutes (based on propofol)propofol)

� 100-140 µg/kg/min for next 2 hours� 80-120 µg/kg/min after 2 hours

Propofol-Ketamine infusion

Reeves JG GlassReeves JG, GlassPSA, Lubarsky DA, McEvoy MD. Intravenous nonopioid anesthetics. In Miller RD. Miller�s Anesthesia 6th ed. 2005

Remifentanil Infusion

Boon to all types of anesthesiaFast onset and recovery; independent of

infusion durationTurn pump on at 1 µg/kg/min

Also start propofol bolus via pump, or wait 30 sec to injectto injectMaintain at 0.1-0.3 µg/kg/min for target plasma concentration of 5ng/mlgTurn off 5-7 min before extubation. Extubate quickly upon awakening

Propofol-Alfentanil TIVA

Induce P f l 0 5 1 /kPropofol 0.5-1mg/kg Alfentanil 25-50 µg/kg

MaintenancePropofol 100-180 µg/kg/minp µg gAlfentanil 0.5-2 µg/kg/min

Dosages loosely suggested; account for level of stimulation and concurrent meds i.e., midazolam

Future of TIVAFuture of TIVA-Esterase Metabolism is in

New hypnotics (THRX-918661/AZD3043)Methoxycarbonyl-etomidateRemimazolam- Sedation with a 6-mg initial

loading dose, then 3-mg doses at >2-minute intervals. Recovery within 16 minutes for 89% of the treated population A th & A l89% of the treated population Anesth & Analg. 2012 Aug;115(2):284-96.

Future of TIVA

Closed-loop anesthesiaDrug advancesDrug advances

S+ ketamine enantiomer Propofol pro-drug

Non-invasive monitoring of propofol blood concentration

It’s all getting so easy but maybe tooIt’s all getting so easy, but maybe tooeasy?

FDA G t P k t A lFDA Grants Premarket ApprovalFor The SEDASYS

May 3, 2013initiation and maintenance of minimal-to-

moderate sedationASA physical status I and II patients > 18

years old colonoscopy and EGDintroduced on a limited basis beginning in

2014

Summary

TIVA techniques can provide numerous advantages over volatile based anestheticsover volatile-based anesthetics.While equipment set-up and cost is greater than using existing vaporizers, long-term savings can be appreciatedappreciated.Context-sensitive PK considerations allow safe and effective narcotic dosing.Modern infusion technology and TCI lends control toModern infusion technology and TCI lends control toIV techniques to rival vaporizer use. More info: UK Society for Intravenous Anaesthesia www sivauk orgwww.sivauk.org